Salvage Surgery in Patients with Local Recurrence After Radical Prostatectomy - Beyond the Abstract

In prostate cancer (PCa), recurrences are frequently observed even after curatively intended primary treatment such as radical prostatectomy (RP). Since the introduction of prostate-specific membrane antigen (PSMA)-positron emission tomography (PET) imaging, these recurrences may be accurately delineated, even at very low prostate-specific antigen (PSA) levels.1 This non-invasive means to assess recurrences creates the opportunity to more accurately apply local salvage therapies. As a consequence, PSMA PET imaging is now recommended prior to treatment decisions in men with biochemical recurrence (BCR) if the results will influence subsequent treatment decisions.2


However, in some patients, local recurrence may be observed even after local salvage radiation therapy (RT) post RP. Here, local treatment options are extremely limited.

In consequence, we aimed at describing and evaluating our technique for open salvage surgery in patients with local recurrence in the area of the former seminal vesicles for the first time. We examined biochemical response, therapy-free survival, as well as complication rates after this procedure.

Overall, 40 consecutive patients were treated with salvage surgery in two centers between November 2014 and February 2020 and included in this retrospective analysis. All patients presented with BCR after initial RP with a singular local recurrence (retrovesical/seminal vesicles bed) at PSMA PET imaging. To facilitate intraoperative targeting of the local recurrence and to confirm successful surgical removal immediately at the operating room (OR) table, we made use of the PSMA-overexpression of most PCa tissue by adopting the PSMA radio-guided surgery approach that had only until now been described in salvage lymph node surgery.3,4

The rate of complete biochemical response (cBR, defined as PSA < 0.2 ng/ml) without additional treatment was determined 6–16 weeks following salvage surgery. Furthermore, BCR-free survival (defined as PSA < 0.2 ng/ml without further treatment) and therapy-free survival (treatment-free survival [TFS], defined as survival without further treatment) were evaluated. Postoperative complications were classified according to Clavien-Dindo.5

The median time from initial primary RP to salvage surgery was 8.5 years. Previous RT was administered in 33 (82.5%) patients. The median time from the last treatment (RT) to salvage surgery was 6.4 years.

Prior to salvage surgery, the median PSA was 0.9 ng/ml. After histological work-up, all removed specimens showed PCa tissue. Post salvage surgery, median PSA nadir was 0.1 ng/ml. In 31 patients (77.5%) a cBR was observed. During the median follow-up of 24.4 months, 22 (55.0%) patients experienced BCR, and 12 (30.0%) patients received further therapy (6x hormonal therapy, 3x radiation therapy, 2x salvage lymphadenectomy, 1x combined chemohormonal therapy).

In Kaplan-Meier analyses, the median BCR-free survival was 23.7 months. At 1 year of follow-up, BCR-free survival rate was 62.2%. Median TFS was 46.3 months. At 1 year of follow-up, TFS rate was 88.3%.

Overall, seven complications (17.5%) were observed. All of these patients were pre-irradiated. Of those, four (10%) were Clavien-Dindo Grade I complications (obstipation, neuropathy, hematoma, residual urine) and three (7.5%) were Clavien-Dindo Grade III complications (suprapubic catheterization, secondary rectal wall necrosis, ureteral injury). No grade IV or V complications were observed.

In patients with local recurrence after salvage RT post RP, local treatment options are extremely limited. Several small series with heterogeneous retrospective cohorts reported interesting results of salvage re-irradiation.6,7 However, to date salvage surgery for local recurrence after RP has not been described nor results been assessed. In consequence, we evaluated PSMA-directed salvage surgery and examined oncological outcomes, as well as complication rates after this procedure for the first time. Our analyses demonstrated that salvage surgery of local recurrence within the seminal vesicle bed is feasible with acceptable complication rates. It may present an opportunity in highly selected, locally recurrent patients to prolong BCR-free survival and increase TFS. Further studies are needed to confirm our findings. The main limitation is the retrospective design, short follow-up, and lack of a control group.

Written by: Sophie Knipper, MD, Tobias Maurer, MD, Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany

References:

  1. Fendler, Wolfgang P., Jeremie Calais, Matthias Eiber, Robert R. Flavell, Ashley Mishoe, Felix Y. Feng, Hao G. Nguyen et al. "Assessment of 68Ga-PSMA-11 PET accuracy in localizing recurrent prostate cancer: a prospective single-arm clinical trial." JAMA oncology 5, no. 6 (2019): 856-863.
  2. European Association Urology. European Association of Urology Guidelines. 2019 Edition. [Internet]. European Association of Urology Guidelines Office, editor. Vol. presented at the EAU Annual Congress Barcelona 2019. Arnhem, The Netherlands: European Association of Urology Guidelines Office; 2019. Available from: http://uroweb.org/guidelines/compilations-of-all-guidelines/
  3. Maurer, Tobias, Stephanie Robu, Margret Schottelius, Kristina Schwamborn, Isabel Rauscher, Nynke S. van den Berg, Fijs WB van Leeuwen et al. "99mTechnetium-based prostate-specific membrane antigen–radioguided surgery in recurrent prostate cancer." European urology 75, no. 4 (2019): 659-666.
  4. Maurer, Tobias, Matthias Eiber, Markus Schwaiger, and Jürgen E. Gschwend. "Current use of PSMA–PET in prostate cancer management." Nature Reviews Urology 13, no. 4 (2016): 226-235.
  5. Clavien, Pierre A., Jeffrey Barkun, Michelle L. De Oliveira, Jean Nicolas Vauthey, Daniel Dindo, Richard D. Schulick, Eduardo De Santibañes et al. "The Clavien-Dindo classification of surgical complications: five-year experience." Annals of surgery 250, no. 2 (2009): 187-196.
  6. Olivier, Jonathan, Laurent Basson, Philippe Puech, Thomas Lacornerie, Arnauld Villers, Jennifer Wallet, Eric Lartigau, and David Pasquier. "Stereotactic re-irradiation for local recurrence in the prostatic bed after prostatectomy: preliminary results." Frontiers in oncology 9 (2019): 71.
  7. Jereczek-Fossa, Barbara Alicja, Damaris Patricia Rojas, Dario Zerini, Cristiana Fodor, Anna Viola, Giuseppe Fanetti, Stefania Volpe et al. "Reirradiation for isolated local recurrence of prostate cancer: Mono-institutional series of 64 patients treated with salvage stereotactic body radiotherapy (SBRT)." The British Journal of Radiology 92, no. 1094 (2019): 20180494.
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